Association of Cigarette Smoking, COPD, and Lung Cancer With Expression of SARS-CoV-2 Entry Genes in Human Airway Epithelial Cells

Junping Yin; Brigitte Kasper; Frank Petersen; Xinhua Yu

doi:10.3389/fmed.2020.619453

Association of Cigarette Smoking, COPD, and Lung Cancer With Expression of SARS-CoV-2 Entry Genes in Human Airway Epithelial Cells

Front Med (Lausanne). 2020 Dec 4:7:619453. doi: 10.3389/fmed.2020.619453. eCollection 2020.

Authors

Junping Yin¹, Brigitte Kasper¹, Frank Petersen¹, Xinhua Yu¹

Affiliation

¹ Division of Pulmonary Immune Diseases, Department of Asthma and Allergy, Research Center Borstel, Leibniz Lung Center, Borstel, Germany.

Abstract

SARS-CoV-2 enters into human airway epithelial cells via membrane fusion or endocytosis, and this process is dependent on ACE2, TMPRSS2, and cathepsin L. In this study, we examined the expression profiles of the three SARS-CoV-2 entry genes in primary human airway epithelial cells isolated from smokers, non-smokers, patients with chronic obstructive pulmonary disease or lung cancer. An exhaustive search of the GEO database was performed to identify eligible data on 1st June 2020. In total, 46 GEO datasets comprising transcriptomic data of 3,053 samples were identified as eligible data for further analysis. All meta-analysis were performed using RStudio. Standardized mean difference was utilized to assess the effect size of a factor on the expression of targeted genes and 95% confidence intervals (CIs) were calculated. This study revealed that (i) cigarette smoking is associated with an increased expression of ACE2 and TMPRSS2 and a decreased expression of cathepsin L; (ii) significant alternations in expression of ACE2, TMPRSS2, and cathepsin L were observed between current smokers and former smokers, but not between former smokers and never smokers; (iii) when compared with healthy controls with identical smoking status, patients with COPD or lung cancer showed negligible changes in expression of ACE2, TMPRSS2, and cathepsin L. Therefore, this study implicates cigarette smoking might contribute to the development of COVID-19 by affecting the expression of SARS-CoV-2 entry genes, while smoking cessation could be effective to reduce the potential risk.

Keywords: ACE2 (angiotensin converting enzyme-2); COVID-19; SARS-CoV-2; cathpesin L; human airway epithelial cells; smoking; transmembrane serine protease 2.